Summary. Atherosclerosis is indicated by the American Heart Association as a primary factor in three fourths of deaths resulting from cardiovascular disease. It is now recognized that many coronary events and strokes are caused by atherosclerotic plaques that rupture - vulnerable plaques. It is important that the cardiologist be able to assess the risk of plaque rupture when diagnosing and treating persons with atherosclerosis. Currently available imaging tools (angioscopy, MRI, intravascular ultrasound) do not provide the high spatial resolution needed for this application. We propose to develop a rapid, high resolution optical imaging method for imaging of venous and arterial structures that will aid in the diagnosis of atherosclerosis, specifically in identifying vulnerable plaques. The new technique, which we call complex differential spectral interferometry (CDSI), will be an important improvement to optical coherence tomography (OCT). It will provide video-rate cross-sectional imaging and will have higher dynamic range than standard time domain OCT. It will be fully compatible with fiber optics allowing incorporation into endoscopes, catheters and similar devices for in vivo applications. In Phase I, we achieved a breakthrough in the development of CDSI (also known as complex Fourier domain OCT). The newly developed version resolves the problem of the complex conjugate ambiguity (one of the main drawbacks of Fourier domain OCT) in an elegant and exceptionally efficient way, which provides a two-fold increase of the maximum imaging depth. In Phase II, the new technique will be used with a novel detector, recently designed and built at Southwest Sciences. The proposed technology takes full advantage of parallel detection inherent in CDSI allowing the greater dynamic range and sensitivity of Fourier domain OCT to be realized. Relevance. Cardiovascular disease affects over 61 million Americans and is the leading cause of death in the US. The major risk is associated with atherosclerotic plaques that rupture - vulnerable plaques, - which are difficult to diagnose with currently available methods. The proposed technology will aid in the diagnosis of vulnerable atherosclerotic plaques, thus providing important information for the cardiologist making risk assessments and choosing the best course of treatment, ultimately, saving lives. [unreadable] [unreadable] [unreadable]